Taurine, Mitochondria, and the Heart

Last month, “Shorts” looked at the possible benefits of using taurine, a sulfur-containing amino acid, to prevent vision loss in age-related macular degeneration – but it seems this amino acid also has a protective effect on mitochondria and the heart as well. In their 2021 review article for Molecules, Chian Ju Jong and colleagues report that taurine has a significant role in mitochondrial function.

Taurine, first isolated from ox bile in 1827, is made from methionine or cysteine in the liver. It is found in abundant amounts in the heart, brain, retina, and skeletal muscle. Some animals, such as cats, require high amounts of taurine in their diets (meat and seafood being primary sources). Without it, the animals develop cardiomyopathy and myocardial dysfunction, retinal degeneration leading to blindness, neurological problems, weakened immune response, and gastrointestinal problems. In research studies, taurine-supplemented diets protected the animals from cardiomyopathy, seizure, and retinopathy.

Taurine is known to have a significant role in maintaining mitochondrial function – though its mechanisms of action are not fully understood. It appears to modify mitochondrial tRNA and help synthesize mitochondrial proteins needed for efficient energy production; oxidative stress, created during mitochondria energy production (ATP), declines with taurine. Taurine also regulates intracellular calcium homeostasis necessary for modulating heart contractions as well as for regulating mitochondrial oxidative phosphorylation to produce ATP. In addition, taurine protects against glutamate-induced excitotoxity that can produce mitochondrial damage and neuron cell death.

Taurine has been an approved treatment for people with heart failure in Japan since 1985. More recently, it has also gained Japanese approval for the treatment of stroke-like episodes in people with the mitochondrial disease MELAS Syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes).

According to Japanese studies, taurine supplementation (2-3 grams/day for 4-8 weeks) increased cardiac output and stroke volume, ejection fraction, and mean velocity of circumferential fiber shortening in most patients with heart failure. Patients with NYHA class II or III heart failure showed improved exercise capacity after receiving 500 mg of taurine, three times/day for two weeks.

Taurine may also be helpful for patients with metabolic syndrome and type 2 diabetes: “When taurine is supplemented, glucose levels are restored, insulin secretion is enhanced and glucose and lipid metabolism in the mitochondria are stimulated.” Several trials have indicated that taurine supplementation may reduce diabetic complications, such as nephropathy, retinopathy, and neuropathy – although a few have not found benefit.

Given its protective effects on mitochondrial function – and the growing list of disorders linked to mitochondrial dysfunction – taurine deserves more attention.

Chian Ju Jong, Sandal P, Schaffer SW. The Role of Taurine in Mitochondria Health: More Than Just an Antioxidant. Molecules. 2021;26:4913.

Strengthening Inspiratory Muscles to Reduce Blood Pressure

Researchers in Boulder, Colorado, are investigating a new type of exercise for reducing systolic blood pressure: inspiratory muscle strength training (IMST). IMST, originally developed in the 1980s to wean patients off ventilators, consists of breathing in through a hand-held device that provides resistance. “Imaging sucking hard through a straw which sucks back,” writes Lisa Marshall.

In 2016, University of Arizona researchers found just 30 breaths/day with IMST helped people with obstructive sleep apnea rest better and strengthened the diaphragm and other inspiratory muscles; it also had the unexpected effect of lowering systolic blood pressure. The Boulder researchers decided to test the effectiveness of IMST on people with high blood pressure by conducting a six-week, double-blind, randomized, sham-controlled trial.

Thirty-six healthy men and post-menopausal women (aged 50-70 years) were randomly assigned to the high-resistance IMST group (n=18) or the “sham” (control) group (n=18). All participants were instructed in using the POWERbreathe K3 inspiratory muscle training device and told to do “30 inspiratory maneuvers (5 sets of 6, 1-minute rest between sets), six days per week for six weeks.” The device tracked adherence to the protocol.

The resistance provided by the device differed between the two groups and was determined by the individuals’ maximum inspiratory pressure (PIMAX). PIMAX was assessed for each participant using a custom-built pressure transducer (Omega-Dyne). Resistance for people in the control group was set at 15% of their PIMAX for the entire six weeks. In the intervention group, resistance was set higher and gradually increased: 55% of PIMAX during week 1, 65% PIMAX during week 2, and 75% PIMAX for the final four weeks. Each participant’s PIMAX was re-assessed at the beginning of each week.

In addition to blood pressure, vasoendothelial function, arterial stiffness, plasma metabolomics, and blood biomarkers of systemic oxidative stress, antioxidant activity, inflammation, and sympathoadrenal activity as well as fasting serum lipids and plasma glucose were assessed. The researchers also conducted endothelial cell culture experiments using participants’ serum to detect the effect on reactive oxygen species (ROS) production and on nitric oxide (NO) production. These measures were taken at baseline, at the study’s end, and at an optional follow-up for IMST participants that occurred six weeks after the intervention concluded.

High-resistance IMST, which took less than 10 minutes/day, produced several positive effects after six weeks of the exercise; the control group showed no change from baseline in any of the measurements. Systolic blood pressure (SBP) decreased from 135±2 mmHg at baseline to 125±3 mmHg after six weeks of IMST (p<0.01). At the optional follow-up, SBP was 128±4 mmHg (p<0.01) in the 15 IMST participants who took part. This decline is greater than or equal to reductions observed with 150 minutes/week of moderate-intensity aerobic exercise. Moreover, the SBP reduction is associated with a 30%-40% lower risk of cardiovascular-related death.

Vascular endothelial function increased about 45% over baseline in the IMST group (p<0.01); but it returned to baseline in the follow-up.

For the most part, blood biomarkers showed no changes from baseline or between the two groups. C-reactive protein, a marker of systemic inflammation, was the exception. It decreased 30% after IMST: baseline 1.37±0.23 mg/L, end-intervention 0.96±0.17 mg/L; P=0.05.

The cell culture experiments showed that NO bioavailability (from increased endothelial NO synthase activation and decreased oxidative stress) was significantly greater after IMST training (p=0.01) and ROS bioactivity decreased (p=0.01).

No changes were observed in arterial stiffness measures, possibly due to the study’s short length.

Neck muscle soreness (n=1) and lightheadedness (n=1) – both of minor severity – were the only treatment-related adverse effects. Adherence to the protocol was excellent: “The IMST group completed 94.4% of prescribed training sessions, whereas the sham group completed 90.0% of prescribed training sessions.”

The authors write:

The results from this pilot study will need to be confirmed in a larger trial, perhaps with a longer treatment duration. It is possible that a longer-term training stimulus would produce even greater improvements in cardiovascular function….

Our results provide support for high-resistance IMST as a promising lifestyle intervention for improving cardiovascular function and possibly decreasing the risk of CVD and other clinical disorders, such as cognitive dysfunction and chronic kidney disease.

Craighead DH, et al. Time-Efficient Inspiratory Muscle Strength Training Lowers Blood Pressure and Improves Endothelial Function, NO Bioavailability, and Oxidative Stress in Midlife/Older Adults With Above-Normal Blood Pressure. J Am Heart Assoc. 2021;10:e020980.

Marshall L. Novel 5-minute workout improves blood pressure, may boost your brain. www.colorado.edu/today/. February 25, 2019.

Pfizer Whistleblower Lawsuit

In the January 2022 issue of Townsend Letter, publisher Jonathan Collin, MD, wrote about the British Medical Journal (BMJ) investigative report about methodological irregularities and data fraud that occurred at Ventavia, one of the test sites for Pfizer’s COVID-19 vaccine. Brook Jackson, a trained clinical trial auditor with over 15 years’ experience, worked as regional director at Ventavia Research Group for two weeks. She was fired in September 2020, after emailing a complaint to the US Food and Drug Administration when her superiors ignored the many data integrity issues that she had observed. Jackson provided investigative reporter Paul D. Thacker and BMJ with documentation (internal company documents, photos, audio recordings, and emails) that supported her allegations of falsified data, unblinded patients, inadequately trained vaccinators, and inadequate follow-up on adverse events in the Pfizer Phase III trial that led to its emergency use authorization.

In January 2021, a few months after being fired, Jackson filed a lawsuit against Pfizer, ICON PLC, (the Irish clinical research organization that was overseeing Pfizer’s 160+ test sites), and Ventavia Research Group, LLC, under the Federal False Claims Act. The False Claims Act, passed during the US Civil War, allows whistleblowers to file lawsuits on behalf of the government against contractors who commit fraud; if fraud is proven and damages are recovered, the whistleblower(s) received a percentage of the money. According to the lawsuit, the US Department of Defense signed a contract with Pfizer to buy “100 million doses of the vaccine for $1.95 billion following FDA approval or Emergency Use Authorization (“EUA”).”

Jackson’s complaint remained under seal (available only to the judge, US attorney general and a few members of the Department of Justice) until February 10, 2022, at which time US District Court Judge Michael Truncale (Eastern District of Texas, Beaumont Division) allowed the lawsuit to be served on the defendants. The judge also released over 400 pages of exhibits to public view (posted in The Epoch Times article). The US Department of Justice has declined to take part on her behalf at this point but may intervene later. Jackson told The Epoch Times, that even though her case may not succeed,“’
[i]t’s just a chance I have to take. I just feel like somebody has to be held accountable.’”

Stieber Z. Exclusive: Pfizer Trial Whistleblower Presses Forward With Lawsuit Without US Government’s Help. The Epoch Times. February 14, 2022.

Thacker PD. Covid-19: Researcher blows the whistle on data integrity issues in Pfizer’s vaccine trial. BMJ. November 2, 2021.

Thiamine Deficiency and Diabetes

Is thiamine (vitamin B1) an important, overlooked factor in diabetes? In a 2021 perspective paper, three Italian researchers report that thiamine has been linked to diabetes as far back as the 1940s and that addressing thiamine deficiency with supplementation improved symptoms of diabetic neuropathy in pilot studies. Thiamine is required for ATP production; it is an essential cofactor of glucose metabolism. It also modulates neuronal and neuro-muscular transmission. Severe thiamine deficiency results in beriberi and affects neurological function.

Beriberi and thiamine deficiency are believed to be rare in the US and other countries with food fortification programs (adding thiamine, niacin, riboflavin and other nutrients to flour). However, in an excellent 2021 article, Chandler Marrs and Derrick Lonsdale explain the biological effects of thiamine deficiency and why it is “hiding in plain sight.”

Thiamine is found in many whole foods, including pork, salmon, trout, tuna, catfish, nuts (macadamia, pistachios), sunflower and flax seeds, navy and black beans, black-eyed peas, lentils, tofu, and brown rice; and the Recommended Dietary Allowance (RDA) to prevent beriberi is just 1.1 mg for adult females and 1.2 for adult males. But eating thiamine-rich foods is just one aspect of avoiding deficiency. Processed high-calorie foods, with increased sugars and chemical additives increase the need for more thiamine. The enzyme that catalyzes thiamine into its active form requires magnesium. Magnesium deficiency is common and can lead to “functional thiamine deficiency,” even when plenty of thiamine is present. Chronic alcoholism contributes to thiamine deficiency, and nicotine in tobacco inhibits thiamine availability. Pharmaceuticals – including metformin, psychiatric medications, metronidazole, trimethoprim, anti-hypertensives, NSAIDS, proton pump inhibitors, and diuretics – can all contribute to a thiamine deficiency.

Marrs and Lonsdale say that early signs of thiamine deficiency are non-specific: uncharacteristic fatigue, hyper-irritability and mood lability, gastrointestinal discomfort and dysmotility, sleep disturbances, and loss of appetite. Several populations have a high incidence of thiamine deficiency, including those with diabetes, psychiatric illness, neurological disorders, and the obese. Late stages of deficiency result in high output cardiac failure and edema (wet beriberi), peripheral neuropathies, muscle pain, and weakness (dry beriberi), or mental confusion, ocular abnormalities and ataxia (Wernicke’s). Because it is difficult to identify, the authors recommend testing for thiamine pyrophosphate (TPP), also called thiamine diphosphate.

Marrs and Lonsdale say, “Given the high rate of metabolic dysfunction observed in western countries, perhaps it is time to redress concepts associated with micronutrient sufficiency and deficiency and reassess diagnostic parameters associated with [thiamine deficiency]….”

Beltramo E, Mazzeo A, Porta M. Thiamine and diabetes: back to the future? Acta Diabetologica. 2021;58:1433-1439.

Marrs C, Lonsdale D. Hiding in Plain Sight: Modern Thiamine Deficiency. Cells. 2021; 10:2595.